Correlation of biofilm formation, virulence factors, and phylogenetic groups among Escherichia coli strains causing urinary tract infection: A global systematic review and meta-analysis.

Background: Different virulence factors are involved in the pathogenesis of urinary tract infection (UTI) caused by Uropathogenic Escherichia coli (UPEC); hence, this study aimed to study the prevalence of biofilm formation, virulence factors, and phylogenetic groups and their correlation with biofilm formation among UPEC isolates through a systematic review and meta-analysis. Materials and Methods: A literature search was conducted from 1, 2000, to the end of 2021 in different databases for studies that reported biofilm together with virulence genes or phylogenetic groups in UPEC isolates from patients with UTI according to PRISMA protocol. Data were analyzed by Comprehensive meta-analysis software. Results: The pooled prevalence of biofilm formers was 74.7%. The combined prevalence of phylogenetic Groups A, B1, B2, and D (s) were reported at 19.6%, 11%, 50.7%, and 20.5%, respectively. The most common virulence genes reported worldwide were fimA, ecpA, and fimH, with a combined prevalence of 90.3%, 86.6%, and 64.9%, respectively. The pooled prevalence of biofilm formation in UPEC isolates with phylogenetic Groups A, B1, B2, D, C, and F were 12.4%, 8.7%, 33.7%, 12.4%, 2.6%, and 2.65%, respectively. Several studies showed a correlation between biofilm production and virulence genes, or phylogenetic groups. Conclusion: Regarding data obtained, the high level of combined biofilm formation (74.7%) and the presence of a positive correlation between biofilm production and virulence genes, or phylogenetic groups as reported by the most studies included in the present review, indicates an important role of biofilm in the persistence of UPEC in the UTI.

Remdesivir Administration in COVID-19 Patients With Renal Impairment: A Systematic Review.

BACKGROUND: Remdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time to clinical improvement of COVID-19 and mortality benefits in patients receiving RDV. The patients with renal disease were excluded from large clinical trials of RDV, and the probable nephrotoxicity of the drug, its metabolites, and the vehicle (sulfobutylether-ß-cyclodextrin) have led to the recommendation against using RDV in patients with an estimated glomerular filtration rate of <30 mL/min. AREAS OF UNCERTAINTY: This systematic review aimed to collect data about the necessity and safety administration of RDV in the setting of renal impairment. DATA SOURCES: Search through databases including MEDLINE, ScienceDirect, Cochrane Library, and PubMed was performed. The studies were carried out in adults and enrolled patients with different types of renal impairment (ie, acute kidney injury, chronic kidney disease, kidney transplant, and renal replacement therapy) were included. Eligible studies were assessed, and required data were extracted. RESULTS: Twenty-two cross-sectional studies, cohorts, case reports, and case series were included in this review. The mortality rate was between 7.3% and 50%, and various severity of COVID-19 was included in the studies. None of them reported an increase in adverse effects attributed to RDV administration. A decrease in inflammatory mediators and other benefits were obvious. CONCLUSIONS: Although the manufacturer's labeling does not recommend RDV administration in patients with severe renal impairment, it seems that nephrotoxicity is less concerning in the population of these patients. Moreover, RDV may be helpful in acute kidney injury induced by the viral invasion of COVID-19. To the best of our knowledge, this is the first systematic review of the use of RDV in kidney failure. Larger, well-designed, and pharmacokinetic studies are required to have a safe and logical recommendation about the use of RDV in patients with renal disorders.

Protective Effects of Intravenous Magnesium Sulfate in Stroke Patients Receiving Amiodarone: A Randomized Controlled Trial.

Anti-arrhythmic agents, like amiodarone, interfere at different stages of the ischemic stroke. However, amiodarone was accompanied with immunological pulmonary complications and adverse neurological effects. We hypothesize that magnesium sulfate in combination with amiodarone holds promise for stroke treatment. Thirty-six patients with confirmed diagnosis of ischemic stroke and atrial fibrillation who received bolus amiodarone were randomly assigned to magnesium sulfate every 24 h or similar volume of normal saline (as placebo) for 5 days. Various severity test scores were used to evaluate the symptoms. Routing biochemistry were also measured at days 1 and 5. Treatment with MgSO4 results in a significant reduction in serum levels of NGAL, Hb, T.Bill, IL-6, IL-8, SNSE, S100B, EGF, PAF, CRP and IgG. Also, MgSO4 treatment significantly improved the RASS, Candida, SOFA, NIHSS and APACHE scores. Moreover, reduction of IL-6, IL-8, SNSE, EGF and APACHE score and increase in RASS score were significantly higher in MgSO4 group compared with placebo. Intravenous administration of MgSO4 in amiodarone-treated stroke patients improved the inflammatory, immunological and neurological indicators and reduced disability in ICU-admitted AIS patients, suggesting that this treatment scheme may prevent amiodarone-induced complications in these patients.

Effects of curcuminoids on inflammatory and oxidative stress biomarkers and clinical outcomes in critically ill patients: A randomized double-blind placebo-controlled trial.

Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU-admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL-6, TNF-α, MCP-1 and CRP were significantly reduced in patients receiving curcuminoids (p < .05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p < .05). The findings of this study suggest that short-term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI.

Evaluation of Epithelial Lining Fluid Concentration of Amikacin in Critically Ill Patients With Ventilator-Associated Pneumonia.

INTRODUCTION: Classically, aminoglycosides are known to have low penetration into the lung tissue. So far, no study has been conducted on human adult patients to evaluate amikacin concentration in epithelial lining fluid (ELF) of the alveoli. Therefore, convincing data are not available from the perspective of pharmacokinetics to support the fact that a dosage of 20 mg/kg of amikacin is sufficient to treat patients with ventilator-associated pneumonia (VAP). METHOD: This was a pilot study of amikacin concentration measurement in the alveolar site of action in critically ill adult patients with VAP who required aminoglycoside therapy. A dose of 20 mg/kg of amikacin was administered over a 30-minute infusion. The serum concentrations of amikacin were evaluated in the first, second, fourth, and sixth hours. However, the ELF concentration of amikacin was evaluated in the second hour with the help of bronchoalveolar lavage sampling technique. RESULTS: A total number of 8 patients was included in the study. The mean (SD) administered dose was 20 (0.9) mg/kg. The mean (SD) peak plasma concentration of amikacin was 59.6 (23) mg/L, with the volume of distribution of 0.36 (0.13)L/kg. The amikacin concentration in ELF was successfully measured in 7 patients (6.3) mg/L. The lung tissue penetration of the drug was described as alveolar percentage, proportional to both the first- and second-hour plasma concentrations, with a mean (SD) of 10.1% (8.4%) and 18% (16.7%), respectively. CONCLUSION: To our knowledge, the current study is the first that investigates whether standard doses of amikacin may lead to sufficient alveolar concentration of the drug. The results show that administration of amikacin in doses of 20 mg/kg in critically ill patients with VAP may not provide sufficient concentrations in ELF.

Effects of supplementation with curcuminoids on serum adipokines in critically ill patients: a randomized double-blind placebo-controlled trial.

Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings.

Vasopressin in Septic Shock; Assessment of Sepsis Biomarkers: A Randomized, Controlled Trial.

BACKGROUND AND AIMS: Vasopressin (VP) in sepsis apart from vasoconstrictive effect may have some immunomodulatory effects. The aim of this study was to evaluate the effect of VP on different aspect of sepsis by measuring of sepsis biomarkers. MATERIALS AND METHODS: In this trial, a total number of 42 septic shock patients were included. The first group received norepinephrine (NE) infusion to reach the target mean arterial pressure (MAP) of ≥ 65 mm Hg and the second group received arginine vasopressin (AVP) infusion in addition to NE. Serum lactate, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, pentraxin 3 (PTX3), angiopoietin 1 and 2 (Ang 1 and 2) levels were assessed. RESULTS: Level of IL-6 and IL-10 decreased, but there was no significant difference between the two groups after 48 h. CRP and PTX3 levels were not also significantly different between groups. Although Angs were not statistically different, there was a trend toward higher Ang-1 in and lower Ang 2 in AVP group after 24 and 48 h. In addition, lactate level did not differ between NE and AVP groups. There was no interaction between VP and hydrocortisone use on IL-6, IL-10, and PTX3, but a significant statistical interaction on Ang 1 and Ang 2 were observed. CONCLUSIONS: Although analysis of sepsis biomarkers showed no significant difference between two groups, no immunomodulatory effect for VP alone, subgroup analysis of hydrocortisone used in this study showed that the combination of glucocorticoids and AVP had a significant effect on Angs level which eventually causes less endothelial permeability and higher MAP in this group of patients.

The Effect of High-dose Parenteral Sodium Selenite in Critically Ill Patients following Sepsis: A Clinical and Mechanistic Study.

INTRODUCTION: Severe sepsis and septic shock is characterized by inflammation and oxidative stress. Selenium levels have been reported to be low due to loss or increased requirements during severe sepsis and septic shock. We investigated the effect of high-dose parenteral selenium administration in septic patients. METHODS: A prospective, randomized control clinical trial was performed in septic patients. After randomization, patients in selenium group received high-dose parenteral sodium selenite (2 mg intravenous [IV] bolus followed by 1.5 mg IV continuous infusion daily for 14 days) plus standard therapy and the control group received standard therapy. The primary endpoint was mortality at 28 days. Changes in the mean levels of high mobility group box-1 (HMGB-1) protein and superoxide dismutase (SOD), duration of vasopressor therapy, incidence of acute renal failure, and 60 days' mortality were secondary endpoints. RESULTS: Fifty-four patients were randomized into selenium group (n = 29) and control group (n = 25). There was no significant difference in 28-day mortality. No significant difference between the two groups with respect to the average levels of HMGB-1 protein and SOD at any point in time over the course of 14 days had observed. CONCLUSION: In early administration within the first 6 h of sepsis diagnosis, our study demonstrated that high-dose parenteral selenium administration had no significant effect either on 28-day mortality or the mean levels of HMGB-1 and SOD (Trial Registration: IRCT201212082887N4 at WHO Clinical Trial Registry, August 29, 2014).

Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis.

INTRODUCTION: Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients. METHODOLOGY: We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality. RESULTS: A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72-0.94; P = 0.008;   I (2) =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67-0.91; P = 0.002; I (2) = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33-1.06; P = 0.28; I(2) = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, -0.04-1.02; P = 0.07; I (2) = 0%). CONCLUSION: The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.

Hypertonic saline solution reduces the oxidative stress responses in traumatic brain injury patients.

BACKGROUND: Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress. MATERIALS AND METHODS: Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient's response for 3 days. Serum total antioxidant power (TAP), reactive oxygen species (ROS) and nitric oxide (NO) were measured at baseline and daily for 3 days. RESULTS: Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively). Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively). During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004). CONCLUSION: Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients.

Successful management of severe generalized tetanus in a 23-year man with phenobarbital adjuvant: A case report.

Generalized tetanus is still a global concern with a mortality rate of up to 50%, especially in low and middle-income countries. We reported a 23-year-old man from Afghanistan admitted to emergency department, with the chief complaint of generalized severe spasms and lockjaw. The patient had skin lesions and had never been vaccinated against tetanus. He intubated and admitted to the intensive care unit (ICU) with diagnose of severe generalized tetanus. After receiving tetanus immunoglobulin and intravenous metronidazole, a combination therapy of midazolam, propofol, atracurium, and morphine was administered. Due to the refractory muscular spasms intravenous phenobarbital started and little by little recovery was achieved. The patient receiving the first two doses of the Td vaccine, and discharged on Day 42 of hospitalization with no symptom recurrence. This case management showed adding phenobarbital to severe tetanus treatment regimen could significantly reduce refractory spasm caused by tetanus, also decrease other medication requirement.

The predictive value of resting heart rate following osmotherapy in brain injury: back to basics.

BACKGROUND: The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia.To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS). METHOD: By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed. RESULTS: After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07). CONCLUSION: Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury.

Comparison of hypertonic saline versus normal saline on cytokine profile during CABG.

BACKGROUND AND THE PURPOSE OF THE STUDY: Blood contact with artificial surfaces of the extracorporeal circuit and ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients. METHODS: The present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA. RESULTS AND MAJOR CONCLUSION: Patients received HS had lower levels of IL-6 and higher level of IL-10 compared with NS group, however these differences were not statistically significant. Results of this study suggest that pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response following CABG operation.

Randomized trial of the effect of intravenous paracetamol on inflammatory biomarkers and outcome in febrile critically ill adults.

BACKGROUND AND THE PURPOSE OF THE STUDY: The febrile reaction is a complex response involving immunologic and other physiologic systems. Antipyretics are commonly used in critically ill patients with fever. We investigated the inflammatory responses following application of antipyretic therapy in febrile critically ill patients with Systemic Inflammatory Response Syndrome (SIRS). PATIENTS AND METHODS: In a prospective, randomized controlled study, critically ill patients with fever (T ≥ 38.3°C), SIRS diagnosed within 24 hours of Intensive Care Unit (ICU) admission and Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥10 were randomized into two groups. Upon appearance of fever, one group received intravenous paracetamol 650 mg every 6 hours for 10 days and other group received no treatment unless temperature reached 40°C. Body temperature, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality and infectious complications were recorded. Levels of Interleukin-1 alpha (IL-1α), IL-6, IL-10, Tumour Necrosis Factor alpha (TNFα) and High-Sensitive C-Reactive Protein (HS-CRP) were assessed at baseline and 2, 6 and 24 hours after intervention. RESULTS AND DISCUSSION: During a period of 15-month screening, 20 patients met the criteria and randomized to the control or paracetamol group. Body temperature decreased significantly in the paracetamol group (p = 0.004) and control group (p = 0.001) after 24 hours, but there was no significant difference between two groups at this time point (p = 0.649). Levels of IL-6 and IL-10 decreased significantly (p = 0.025 and p = 0.047, respectively) in the paracetamol group at 24 hours but this was not of statistical significance in control group. No patterns over time in each group or differences across two groups were found for HS-CRP, TNFα, and IL-1α (p > 0.05). There were no differences regarding ICU length of stay, mortality and infectious complications between both groups. CONCLUSION: These results suggest that antipyretic therapy may not be indicated in all ICU patients. Allowing fever to take its natural course does not appear to have detrimental effects on critically ill patients with SIRS and may avoid unnecessary expenses.

Positive effect of septimeb™ on mortality rate in severe sepsis: a novel non antibiotic strategy.

BACKGROUND: Septimeb is a new herbal-derived remedy, recently approved for its potential immunomodulatory effects. Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients; we evaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis. METHODS: In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II) score of more than 20 to receive standard treatment of severe sepsis (control group) or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-α, total antioxidant power, platelet growth factor and matrix metalloproteinase 2. RESULTS: A total of 29 patients underwent randomization (13 in control group and 16 in Septimeb group). There was significant difference between the Septimeb and control group in the 14 days mortality rate (18.8% vs. 53.85 respectively, P=0.048). Compared to control group, Septimeb was significantly effective in improving SAPS (P= 0.029), SOFA (P=0.003) and APACHE II (P=0.008) scores. Inflammatory biomarkers didn't change significantly between the two groups (P>0.05). CONCLUSION: Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis.

Effects of angiotensin receptor blockers (ARBs) on clinical outcomes of patients with hypertension and COVID-19: A 7-month follow-up cohort study.

Introduction: Since the coronavirus disease 2019 (COVID-19) pandemic, the use of angiotensin II receptor blockers (ARBs) in hypertensive patients with COVID-19 has been controversial. Following our previous study, after one year, we intended to extend our sample size and results to investigate the effects of ARBs with both in-hospital outcomes and 7-month follow-up results in patients with COVID-19. Methods: Patients with a diagnosis of COVID-19 who were admitted to Sina Hospital, Tehran, Iran, from February to October 2020 participated in this follow-up cohort study. The COVID-19 diagnosis was based on a positive polymerase chain reaction test or chest computed tomography scan according to guidelines. Patients were followed for disease severity, incurring in-hospital mortality, complications, and 7-month all-cause mortality. Results: We evaluated 1413 patients with COVID-19 in this study. After excluding 124 patients, 1289 including 561(43.5%) hypertensive patients, entered the analysis. During the study, 875(67.9%) severe disease, 227(17.6%) in-hospital mortality, and 307(23.8%) 7-month all-cause mortality were observed. After adjusting for possible confounders, ARB was not associated with severity, in-hospital and 7-month all-cause mortality, and in-hospital complications except for acute kidney injury. Discontinuation of ARBs was significantly associated with higher in-hospital mortality and 7-month all-cause mortality (both P values<0.006). We observed a better 7-month outcome in those who continued their ARBs after discharge. Conclusion: The results of this study, along with the previous studies, provide reassurance that taking ARBs is not associated with the risk of mortality, complications, and poorer outcomes in hypertensive COVID-19 patients after adjustment for possible confounders.

Efficacy of Glucocorticoid Administration in Patients with Cardiac Arrest: A Systematic Review of Clinical Studies.

BACKGROUND: The pathophysiology of cardiac arrest (CA) involves over-activation of systemic inflammatory responses, relative adrenal insufficiency, and glycocalyx damage. Corticosteroids have beneficial effects in preventing the perturbation of the endothelial glycocalyx. OBJECTIVES: The aim of this systematic review was to determine the efficacy of glucocorticoids in patients with cardiac arrest. METHODS: We searched PubMed, Scopus, ISI Web of Science, Google Scholar, and Cochrane central register for relevant clinical trials and cohort studies until September 2019. RESULTS: We retrieved 7 peer-reviewed published studies for the systematic review. Two studies were clinical trials evaluating 147 patients, while five illustrated cohort design, evaluating 196,192 patients. In total, 196,339 patients were assessed. There was limited evidence and conflicting results to establish a correlation between glucocorticoids and the survival of patients suffering from cardiac arrest. However, the links between these medications and survival-to-admission, survival-to discharge, and 1-year survival rates were strong and consistent in observational studies. CONCLUSION: The clinical evidence regarding the efficacy and safety of glucocorticoids in CA is limited to observational studies with inconsistent methodology and few clinical trials with a small sample size. Nevertheless, it seems that glucocorticoid supplementation during and after cardiopulmonary resuscitation (CPR) may have beneficial effects in terms of survival-to-admission, survival to discharge, 1-year survival rates, and an improved return of spontaneous circulation (ROSC) rate, especially in patients with hemodynamic instability and cardiovascular diseases (i.e., refractory hemodynamic shock). Future studies with high-quality, large-scale, long-term intervention and precise baseline characteristics are needed to evaluate the exact effective dose, duration, and efficacy of glucocorticoids in CA.

Predictors of Mortality among COVID-19 Patients Admitted to Intensive Care Units: A Single-Center Study in Tehran, Iran.

BACKGROUND: Iran was one of the first countries to become an epicenter of the coronavirus disease 2019 (COVID-19) epidemic. However, there is a dearth of data on the outcomes of COVID-19 and predictors of death in intensive care units (ICUs) in Iran. We collected extensive data from patients admitted to the ICUs of the one of the tertiary referral hospitals in Tehran, Iran, to investigate the predictors of ICU mortality. METHODS: The study population included 290 COVID-19 patients who were consecutively admitted to the ICUs of the Sina hospital from May 5, 2021, to December 6, 2021, a period that included the peak of the epidemic of the delta (δ) variant. Demographic data, history of prior chronic diseases, laboratory data (including markers of inflammation), radiologic data, and medication data were collected. RESULTS: Of the 290 patients admitted to the ICUs, 187 (64.5%) died and 103 (35.5%) survived. One hundred forty-one (141, 48.6%) were men, and the median age (10th percentile, 90th percentile) was 60 (41, 80). Using logistic regression models, older age, history of hypertension, high levels of inflammatory markers, low oxygen saturation, substantial lung involvement in computed tomography (CT) scans, and gravity of the disease as indicated by the WHO 8-point ordinal scale were primary predictors of mortality at ICU. The use of remdesivir and imatinib was associated with a statistically non-significant reduction in mortality. The use of tocilizumab had almost no effect on mortality. CONCLUSION: The findings are consistent with and add to the currently existing international literature. The findings may be used to predict risk of mortality from COVID-19 and provide some guidance on potential treatments.

Pharmacokinetic study of high-dose oral rifampicin in critically Ill patients with multidrug-resistant Acinetobacter baumannii infection.

PURPOSE: Although rifampicin (RIF) is used as a synergistic agent for multidrug-resistant Acinetobacter baumannii (MDR-AB) infection, the optimal pharmacokinetic (PK) indices of this medication have not been studied in the intensive care unit (ICU) settings. This study aimed to evaluate the PK of high dose oral RIF following fasting versus fed conditions in terms of achieving the therapeutic goals in critically ill patients with MDR-AB infections. METHODS: 29 critically ill patients were included in this study. Under fasting and non-fasting conditions, RIF was given at 1200 mg once daily through a nasogastric tube. Blood samples were obtained at seven time points: exactly before administration of the drug, and at 1, 2, 4, 8, 12, and 24 h after RIF ingestion. To quantify RIF in serum samples, high-performance liquid chromatography (HPLC) was used. The MONOLIX Software and the Monte Carlo simulations were employed to estimate the PK parameters and describe the population PK model. RESULTS: The mean area under the curve over the last 24-h (AUC0-24) value and accuracy (mean ± standard deviation) in the fasting and fed states were 220.24 ± 119.15 and 290.55 ± 276.20 µg × h/mL, respectively. There was no significant difference among AUCs following fasting and non-fasting conditions (P > 0.05). The probability of reaching the therapeutic goals at the minimum inhibitory concentration (MIC) of 4 mg/L, was only 1.6%. CONCLUSION: In critically ill patients with MDR-AB infections, neither fasting nor non-fasting administrations of high-dose oral RIF achieve the therapeutic aims. More research is needed in larger populations and with measuring the amount of protein-unbound RIF levels.

Effect of heart rate control with amiodarone infusion on hemodynamic and clinical outcomes in septic shock patients with tachycardia: a prospective, single-arm clinical study.

BACKGROUND: Keeping the heart rate within the normal range has improved the survival of septic shock patients. Amiodarone could target the underlying pathophysiology of sepsis-induced tachycardia. This study aimed to determine whether amiodarone is effective in controlling the heart rate in critically ill patients with septic shock and sustained tachycardia who were receiving vasopressor. METHODS: In this prospective, single-arm cohort study, 46 patients with septic shock and tachycardia were enrolled to receive a loading dose of amiodarone 150 mg, then continuous infusion of 1 mg/min. The primary outcome was the ability of amiodarone in rate control lower than 95 beats per minute (BPM) and maintaining it during 24-h study period. We also recorded the effect of amiodarone on hemodynamic indices as the secondary outcomes. RESULTS: The results of the present study indicated a significant decrease in HR in septic shock patients for amiodarone, from 121.0 (116.5, 140.0) at baseline to 91.5(89.3, 108.0) at the end of the study period (p < 0.001). During the study period, a total of 26 (56.52%) of patients achieved the target heart rate lower than 95 BPM and maintained it during study period. Amiodarone decreased HR by 22.8 ± 13.7. While receiving amiodarone infusion, the values for heart rate, mean arterial pressure, cardiac index, norepinephrine infusion rate, and stroke volume index changed significantly between amiodarone initiation and 24-h follow-up (P < 0.001). Amiodarone was well tolerated, because this anti-arrhythmic agent did not increase the need for vasopressor and none of the patients experienced episodes of refractory hypotension. CONCLUSION: This study showed that amiodarone infusion successfully reduced the heart rate in sepsis-induced tachycardia. The patients had improved hemodynamic state as indicated by an increase in cardiac index and SVI.